Archives of pathology & laboratory medicine最新文献

Context.—: Technology companies and research groups are increasingly exploring applications of generative artificial intelligence (GenAI) in pathology and laboratory medicine. Although GenAI holds considerable promise, it also introduces novel risks for patients, communities, professionals, and the scientific process.

Objective.—: To summarize the current frameworks for the ethical development and management of GenAI within health care settings.

Data sources.—: The analysis draws from scientific journals, organizational websites, and recent guidelines on artificial intelligence ethics and regulation.

Conclusions.—: The literature on the ethical management of artificial intelligence in medicine is extensive but is still in its nascent stages because of the evolving nature of the technology. Effective and ethical integration of GenAI requires robust processes and shared accountability among technology vendors, health care organizations, regulatory bodies, medical professionals, and professional societies. As the technology continues to develop, a multifaceted ecosystem of safety mechanisms and ethical oversight is crucial to maximize benefits and mitigate risks.

Context.—: Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-targeted therapy, has demonstrated durable anticancer activity in patients with advanced, metastatic HER2 (also known as ERBB2)-mutant (HER2m) non-small cell lung cancer (NSCLC) who have limited treatment options and poor prognosis.

Objective.—: To analytically validate and assess the clinical utility of the Oncomine Dx Target (ODxT) Test as a companion diagnostic to identify patients with HER2m NSCLC.

Design.—: Tumor samples from patients in DESTINY-Lung01 and DESTINY-Lung02 were retrospectively analyzed alongside commercially procured samples using the ODxT test and compared to the assays used for screening in these clinical trials.

Results.—: Positive percent agreement (PPA) and negative percent agreement (NPA) between the ODxT Test and TruSight Tumor 170 assay when testing DESTINY-Lung01 and commercially procured samples met prespecified thresholds (PPA and NPA ≥90%) for analytical accuracy (100% and 99.1%). The ODxT Test results were highly concordant with clinical trial assays (CTAs) used in DESTINY-Lung01 (PPA and NPA, 98.0% and 100%) and DESTINY-Lung02 (PPA and NPA, 96.7% and 100%) to identify activating HER2 mutations in tumor samples. Confirmed objective response rates were similar between patients with HER2m tumors identified by the ODxT Test and by CTAs in DESTINY-Lung01 (58.3% and 54.9%) and DESTINY-Lung02 (53.6% and 53.8%). Response duration was 12.0 and 9.3 months for patients identified by the ODxT Test and CTAs, respectively, in DESTINY-Lung01.

Conclusions.—: The ODxT Test detected HER2 mutations in NSCLC with high analytical and clinical accuracy and identified HER2m populations with response rates similar to populations identified by CTAs, supporting clinical utility of the ODxT Test to inform treatment decisions for HER2m NSCLC.

Context.—: A positive association between antithrombin activity and selenium level was reported. Selenoprotein P, the most important selenium carrier, was identified within human plasma fibrin clots.

Objective.—: To investigate the relationship between selenoprotein P and antithrombin and its role in modulation of fibrin clot properties in antithrombin-deficient patients.

Design.—: Proteomic analysis of plasma fibrin clots was performed with mass spectrometry. In 108 patients with genetically confirmed type I (57%) or type II (43%) antithrombin deficiency and in healthy controls (n = 50), we assessed plasma selenoprotein P levels and thiobarbituric acid-reactive substances by enzyme-linked immunosorbent assay, along with fibrin clot permeability, clot lysis time, and thrombin generation.

Results.—: Clot-bound antithrombin concentration was 0.46 ± 0.32 mg/g protein, while selenoprotein P level was 30-fold lower (0.015 ± 0.012 mg/g). Type I compared to type II antithrombin-deficient patients had higher clot-bound antithrombin and selenoprotein P levels (both P < .001), associated together (ρ = 0.93, P < .001). Individuals with type I compared to type II antithrombin deficiency or controls had about 40% lower plasma selenoprotein P levels (P < .001). In antithrombin-deficient patients, plasma selenoprotein P was associated with antithrombin antigen (ρ = 0.35, P < .001) and thiobarbituric acid-reactive substances (ρ = 0.42, P < .001). Plasma selenoprotein P correlated also with endogenous thrombin potential (r = -0.33, P < .001), fibrin clot permeability (r = 0.43, P < .001), and clot lysis time (r = -0.40, P < .001) in antithrombin-deficient patients but not in controls.

Conclusions.—: Patients with type I antithrombin deficiency had higher clot-bound selenoprotein P and reduced plasma selenoprotein P levels. Plasma selenoprotein P was associated with prothrombotic fibrin clot phenotype and enhanced thrombin generation.

Context.—: Challenges to staffing a high-quality frozen section service include consolidation of health systems and pathology practices, off-campus relocation of some pathology offices, growing numbers of stand-alone surgery centers, and subspecialization among pathologists and surgeons. To address these challenges, we developed a novel anatomic pathology hospitalist model with explicit emphasis in frozen section.

Objective.—: To evaluate our anatomic pathology hospitalist program's impact on (1) frozen section staffing, (2) frozen-permanent diagnostic concordance, and (3) turnaround time.

Design.—: Frozen section staffing and performance data were collected for the 28-month period spanning July 1, 2021, to October 31, 2023. Outcomes were compared between hospitalists, nonhospitalists, and fellows.

Results.—: Hospitalists performed more frozen sections per month than nonhospitalists (median, 87 versus 17, respectively; P = .002). After implementation, nonhospitalists' average frozen section staffing obligation fell from 3.7 (30%) of 12.3 total service days per month to 2.8 (22%) of 12.6 total service days per month (P = .005), compared with hospitalists' average of 9.5 frozen section days (69%) of 13.7 total service days per month. Frozen-permanent concordance was marginally but significantly higher for hospitalists (4701 of 4744 blocks, 99.1%) than nonhospitalists (7259 of 7362 blocks, 98.6%; P = .02). Concordance did not correlate with pathologists' academic rank or subspecialization. Turnaround times were comparable for hospitalists, nonhospitalists, and fellows across multiple metrics.

Conclusions.—: Our anatomic pathology hospitalists significantly reduced the frozen section obligations of nonhospitalist faculty, with a small but significant increase in frozen-permanent concordance and no substantial change in turnaround time.

Context.—: Many drugs can induce liver injury; however, vaccine-induced liver injury is a rare phenomenon. SARS-CoV-2 messenger RNA (mRNA) vaccines are now widely administered, and clinical evidence of liver injury has been reported.

Objective.—: To characterize the histologic features of SARS-CoV-2 mRNA vaccine-associated liver injury.

Design.—: Thirteen liver biopsies from 12 patients with elevated liver enzymes clinically favored to be secondary to SARS-CoV-2 mRNA vaccine were identified between 2021 and 2022. Demographics, clinical information, and histologic features of liver biopsies were reviewed.

Results.—: All patients (median age, 58 years; M:F = 4:8) received at least 1 dose of SARS-CoV-2 mRNA vaccines (7 Pfizer and 5 Moderna). Four patients had a history of liver disease. Nine patients developed symptoms between 1 day and 2 months after receiving the vaccine dose. Viral serologies were negative. Drug-induced liver injury was thought to be less likely clinically in the 3 patients who had started new medications. Autoimmune antibodies were detected in 9 patients. Moderate to severe active hepatitis was the dominant histologic pattern of injury (9 of 13 biopsies; 69%). Resolving hepatitis, cholestatic hepatitic injury, and bile duct injury were identified in 1 biopsy each. All patients recovered spontaneously or with steroid therapy except one patient who developed autoimmune hepatitis.

Conclusions.—: Moderate to severe active hepatitis is commonly observed in SARS-CoV-2 mRNA vaccine-associated liver injury, and female patients may be more susceptible to injury. Liver injury resolves spontaneously or with steroid treatment. In rare cases, these vaccines may trigger an underlying immune condition.

Context.—: Gastrointestinal manifestations of Kaposi sarcoma are rare but may cause morbidity. Lower gastrointestinal involvement is particularly rare and lesions may resemble conventional bowel polyps.

Objective.—: To study 15 patients who presented with lower gastrointestinal tract Kaposi sarcoma with polypoid architecture.

Design.—: The surgical pathology files of the departments of pathology at multiple institutions were searched for cases of Kaposi sarcoma forming polyps in the lower gastrointestinal tract (jejunum, colon, rectum); 15 cases with such features were identified. Clinicopathologic information was extracted from the medical record and documented by reviewing individual hematoxylin-eosin stained slides.

Results.—: The patients were 13 men and 2 women aged 26-80 years (median = 44 years). Gastrointestinal tract involvement was multifocal in 11 cases and unifocal in 4. The tumors involved the rectum, recto-sigmoid junction, cecum, ascending colon, transverse colon, and descending colon and presented as polypoid lesions measuring 0.2-2.1 cm. Six patients had upper gastrointestinal tract involvement in addition to lower gastrointestinal lesions. Histologically the tumors were characterized in 6 cases by a dense spindle cell proliferation in the lamina propria; however, the remaining cases showed only a subtle fascicular spindle cell proliferation in the lamina propria that did not form an expansile mass.

Conclusions.—: Biopsies of gastrointestinal polyps showing absence of the common features of hyperplastic or adenomatous polyps, particularly in immunocompromised patients, should be carefully examined for the presence of a stromal spindle cell proliferation. Use of immunohistochemical stains, particularly human herpesvirus-8, can help in establishing the correct diagnosis.

Context.—: Urothelial denudation seen in transurethral biopsy specimens may occasionally indicate the presence of discohesive high-grade urothelial carcinoma (HGUC).

Objective.—: To determine if denuded urothelial cells can be detected in the supernatants of formalin solution collected from the containers of transurethral biopsy/resection specimens after the entire tissue was submitted for histologic examination.

Design.—: We assessed the formalin supernatants by processing for cell block (n = 43) or ThinPrep smear (n = 57).

Results.—: In the cell block cohort, only 2 of 43 cases (5%) (1 pTa HGUC, 1 pT1 HGUC) showed rare urothelial cells. By contrast, in the ThinPrep method, the smear was satisfactory for evaluation in 52 of 57 cases (91%). The cytologic diagnosis of HGUC was made in the smears from 7 of 12 (58%) pTa/pT1 cases and 6 of 9 (67%) pTis cases. Remarkably, HGUC cells were detected in 2 of 5 cases (40%) with histologic diagnosis of urothelial atypia suspicious for but not diagnostic of urothelial carcinoma in situ. Additionally, in 31 cases exhibiting urothelial denudation without definitive cancer on hematoxylin-eosin-stained slides, HGUC cells (2 of 31; 6%), atypical urothelial cells (5 of 31; 16%), or benign-appearing urothelial cells (20 of 31; 65%) were present, and only 4 of 31 (13%) were unsatisfactory.

Conclusions.—: Cytologic examination of ThinPrep smears from the formalin supernatants even following submission of the entire transurethral biopsy/resection specimens for histologic examination is useful for assessing denuded urothelial cells. This technique can particularly be applied to nonneoplastic cases showing extensive urothelial denudation to detect possible malignant cells and/or indeterminate cases to assist to make a more definitive diagnosis.

Context.—: Gross evaluation of post-neoadjuvant chemotherapy breast carcinoma is challenging when the primary tumor is not localized before therapy with a radio-opaque wire/clip, a situation common in resource-constrained settings.

Objective.—: To compare 2 grossing approaches in post-neoadjuvant chemotherapy breast carcinoma specimens to evaluate the sampling adequacy.

Design.—: Fifty breast carcinoma specimens were grossed in a 2-step manner. Tumor bed was identified using clinico-radiologic and gross correlation and 1 slice was selected as most representative (sample I). Subsequently, the entire tumor bed was submitted in grids of multiple slices (sample II). Agreement between methods was assessed using κ values.

Results.—: Sample I prepared an average of 8 blocks per case while sample II prepared 26 blocks. Pathologic complete response (pCR) by both methods was calculated. Sample I documented 23 cases with pCR of which 21 were confirmed by sample II. The 2 cases missed by sample I had less than 5% residual tumor (residual cancer burden class I). Both cases were human epidermal growth factor receptor 2 (HER2)-positive and residual tumor was seen in the slices adjacent to the selected slice. The concordance between the 2 methods was 94% with κ value of 0.915 for sample I, indicating excellent correlation with sample II.

Conclusions.—: The average cost of sample I was 33% of that of sample II and helped calculate the residual cancer burden with similar accuracy. However, in HER2-positive cases, pCR may be overestimated. Hence, we recommend sampling slices adjacent to the selected tumor slice. Further study using this method is essential due to its limited sample size and single-center design before considering implementation in the general population.

Context.—: In this era of health care challenges, efficient resource use is crucial. Patients with inflammatory bowel disease (IBD) may undergo surgery owing to treatment-refractory disease or strictures. Unlike colorectal cancer resections, there are no guidelines for lymph node retrieval in nonmalignant IBD resections.

Objective.—: To assess the usefulness and cost-effectiveness of extensive lymph node examination in nonmalignant IBD resections.

Design.—: A retrospective analysis of 354 cases from 2011 to 2018 was conducted. Resections for suspected malignancy or lesions grossly suggestive of carcinoma were excluded. Patient data, resection type, lymph node count, and follow-up information were collected.

Results.—: Results showed 51% (180) of cases had 12 or more examined lymph nodes. Only 1 case (0.3%) revealed microscopic invasive carcinoma associated with stricture without metastasis to 26 examined lymph nodes. No metastatic disease was found among the 4972 evaluated lymph nodes. Estimated total savings were at least $19 812, with approximately 10.4 minutes saved on microscopic evaluation. During a mean 5.7-year follow-up, no patients developed metastatic disease from an intestinal primary tumor. Among the 20 deceased patients, cause of death was available for 14 patients (70%), of whom 11 (55%) died of nonneoplastic causes and 3 (15%) of nonintestinal malignancies.

Conclusions.—: While lymph node assessment is crucial in IBD-associated colorectal carcinoma, a colorectal cancer protocol-type lymph node search is unnecessary without clinical or gross pathologic suspicion. A conservative approach to lymph node sampling optimizes resources without compromising patient care.

Context.—: Noninvasive self-sampling is a convenient option that may be highly accepted by women for home-based detection, which could increase the screening rate for cervical cancer (CC) and reduce its incidence and mortality.

Objective.—: To compare the distribution of high-risk human papillomavirus (hr-HPV) between the vulva and cervix and to explore the clinical value of vulvar HPV detection in CC screening.

Design.—: The study was nested within a clinical trial on a recombinant HPV 9-valent vaccine for women ages 20 to 45 years. Women with paired vulvar and cervical specimens were included and underwent cytology and HPV detection. The consistency of HPV detection between vulvar and cervical specimens was evaluated using Cohen κ statistics. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the diagnostic accuracy of primary CC screening. The primary end points were cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+).

Results.—: A total of 7999 women were enrolled, and 83/33 cases were diagnosed as CIN2+/CIN3+. The HPV-positive rate in vulvar specimens (1785 of 7999; 22.32%) was higher than that in cervical specimens (1390 of 7999; 17.38%), and there were no significant differences in the distribution of hr-HPV genotypes between the vulva and cervix in patients with CIN2+/CIN3+. Vulva-based HPV primary screening showed sensitivity, specificity, PPV, and NPV comparable to those for cervix-based HPV primary CC screening in the detection of CIN3+.

Conclusions.—: The distribution of vulvar and cervical HPV was similar in patients with CIN2+/CIN3+. Vulva-based HPV primary CC screening had acceptable diagnostic efficacy and might be used as a modality for primary CC screening.